Pancreatic cancer is one of the most common forms of malignant disease with a poor survival prognosis. Currently, nanomedicine holds great promise for targeted diagnosis and treatment of this cancer, which also reduces toxic side effects. In this work, we prepared PEG-coated monodisperse upconversion nanoparticles (UCNPs) with a conjugated Flamma® fluorescent dye for imaging and detection of particle distribution in vivo. We performed a thorough physicochemical characterization of the particles and determined their colloidal and chemical stability in several aqueous media such as water, PBS, Dulbecco's modified Eagle's medium and artificial lysosomal fluid. Luminescence resonance energy transfer from the emission of UCNPs as a donor to the Flamma® as an acceptor was confirmed. Intraperitoneal versus intravenous administration was then compared in terms of biodistribution of particles in various organs in the orthotopic mice pancreatic cancer model. The intraperitoneal route was preferred over the intravenous one, because it significantly increased the accumulation of particles in the tumor tissue. These new UCNP@Ale-PEG-Flamma® nanoparticles are thus promising for new treatment avenues for pancreatic cancer.
- Publikační typ
- časopisecké články MeSH
A 41-year-old man was admitted to hospital due to sudden loss of consciousness. A regional brain perfusion SPECT/low-dose CT showed abnormal 99m Tc-HMPAO uptake in the right hemisphere frontotemporally without any other supratentorial or infratentorial radiotracer uptake. A neuropathological examination disclosed a middle cerebral artery aneurysm. Presumably, vessel wall fibrosis prevented collapse. Multiple transmural dissections of the fibrotic aneurysmal wall were the source of the subarachnoid hemorrhage. This interesting image shows that radiotracer accumulation in cerebral artery aneurysms can be a diagnostic pitfall in brain death scintigraphy assessment.
PURPOSE: A new generation of CT detectors were recently developed with the ability to measure individual photon's energy and thus provide spectral information. The aim of this work was to assess the performance of simultaneous fat and iron quantification using a clinical photon-counting CT (PCCT) and its comparison to dual-energy CT (DECT), MRS and MRI at 3 T. METHODS: Two 3D printed cylindrical phantoms with 32 samples (n = 12 fat fractions between 0 % and 100 %, n = 20 with mixtures of fat and iron) were scanned with PCCT and DECT scanners for comparison. A three-material decomposition approach was used to estimate the volume fractions of fat (FF), iron and soft tissue. The same phantoms were examined by MRI (6-echo DIXON, a.k.a. Q-DIXON) and MRS (multi-echo STEAM, a.k.a. HISTO) at 3 T for comparison. RESULTS: PCCT, DECT, MRI and MRS computed FFs showed correlation with reference fat fraction values in samples with no iron (r > 0.98). PCCT decomposition showed slightly weaker correlation with FFref in samples with added iron (r = 0.586) compared to MRI (r = 0.673) and MRS (r = 0.716) methods. On the other hand, it showed no systematic over- or underestimation. Surprisingly, DECT decomposition-derived FF showed strongest correlation (r = 0.758) in these samples, however systematic overestimation was observed. FF values computed by three-material PCCT decomposition, DECT decomposition, MRI and MRS were unaffected by iron concentration. CONCLUSIONS: This in-vitro study shows for the first time that photon-counting computed tomography may be used for quantification of fat content in the presence of iron deposits.
- Klíčová slova
- Fat fraction, Iron, MRI, Photon-counting CT,
- MeSH
- algoritmy MeSH
- fantomy radiodiagnostické MeSH
- magnetická rezonanční tomografie metody MeSH
- počítačová rentgenová tomografie * metody MeSH
- železo * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- železo * MeSH
Proteinase-activated receptors (PARs) were discovered more than 25 years ago and since then, their role in cancer has been under investigation. Research has primarily focused on the receptors located on the membrane of cancer cells and their impact on metabolism, intracellular signalling, and proliferation. Regarding the host response to cancer, studies have predominantly examined the relationship of thrombin receptors (PAR-1, PAR-3, and PAR-4) with blood clotting in distant metastatic spread. However, limited studies have examined the role of PARs, especially PAR-2, in the host anti-tumor immunity. This review article provides insights into the role of PAR-2 on cancer cells and immune competent cells involved in cancer development and progression. It also discussed the current knowledge of the importance of PAR-2 activation at various stages of cancer progression and its association with cancer-related pain.
- Klíčová slova
- PAR-2, cancer, fibroblasts, proteinases, review, thrombin, trypsin,
- MeSH
- lidé MeSH
- nádory * metabolismus MeSH
- receptor PAR-1 metabolismus MeSH
- receptor PAR-2 * metabolismus MeSH
- signální transdukce fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- receptor PAR-1 MeSH
- receptor PAR-2 * MeSH
Healthcare data held by state-run organisations is a valuable intangible asset for society. Its use should be a priority for its administrators and the state. A completely paternalistic approach by administrators and the state is undesirable, however much it aims to protect the privacy rights of persons registered in databases. In line with European policies and the global trend, these measures should not outweigh the social benefit that arises from the analysis of these data if the technical possibilities exist to sufficiently protect the privacy rights of individuals. Czech society is having an intense discussion on the topic, but according to the authors, it is insufficiently based on facts and lacks clearly articulated opinions of the expert public. The aim of this article is to fill these gaps. Data anonymization techniques provide a solution to protect individuals' privacy rights while preserving the scientific value of the data. The risk of identifying individuals in anonymised data sets is scalable and can be minimised depending on the type and content of the data and its use by the specific applicant. Finding the optimal form and scope of deidentified data requires competence and knowledge on the part of both the applicant and the administrator. It is in the interest of the applicant, the administrator, as well as the protected persons in the databases that both parties show willingness and have the ability and expertise to communicate during the application and its processing.
- Klíčová slova
- EHDS, GDPR, anonymization, de-identification, health data,
- MeSH
- anonymizace dat * MeSH
- důvěrnost informací * MeSH
- lidé MeSH
- soukromí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
In human-altered landscapes, specialist butterflies typically form spatially restricted populations, genetically differentiated due to dispersal restrictions. Generalists, in contrast, display minimum differentiation but high genetic diversity. While local-level actions suffice to conserve specialists and landscape-level actions are necessary for generalists, minimum information exists regarding conservation of species with intermediate features. We targeted two congeneric butterflies, the recently re-expanding Argynnis adippe and the strongly declining A. niobe, co-occurring in the pastoral landscape of the Carpathian Mountains, Czech Republic. We integrated species distribution models, mark-recapture and microsatellite analysis to compare their habitat requirements, adult demography, dispersal and genetic patterns, and expanded the genetic analysis across the Carpathian Arc and beyond to delimit spatial conservation units. In two mountain valleys, both species formed interconnected populations numbering thousands of individuals. Mobility patterns suggested the populations' interconnection across the Czech Carpathians. Genetic diversity was extremely poor in the nonthreatened A. adippe and moderate in the declining A. niobe. No population differentiation was detected within the Czech Carpathians (~1500 km2 ). Low genetic diversity and no differentiation was preserved in A. adippe across East Central Europe, whereas in A. niobe, populations from Serbia were differentiated from the Carpathian Arc + Alps. The high adult mobility linked to low differentiation probably reflects the distribution of larval resources, historically widespread but sparse and currently declining for A. niobe (grazing-disturbed grounds), while currently increasing for A. adippe (abandonment scrub, disturbed woodlands). Units as large as entire mountain systems define population boundaries, and hence conservation management units, for both species.
- Klíčová slova
- Carpathians, European grasslands, Lepidoptera conservation, Nymphalidae, butterfly ecology, microsatellites, pastoral land use, population differentiation, traditional landscapes,
- MeSH
- demografie MeSH
- ekosystém MeSH
- lidé MeSH
- motýli * genetika MeSH
- populační genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
This updated review aims to describe the current status in the development of liposome-based systems for the targeted delivery of phthalocyanines for photodynamic therapy (PDT). Although a number of other drug delivery systems (DDS) can be found in the literature and have been studied for phthalocyanines or similar photosensitizers (PSs), liposomes are by far the closest to clinical practice. PDT itself finds application not only in the selective destruction of tumour tissues or the treatment of microbial infections, but above all in aesthetic medicine. From the point of view of administration, some PSs can advantageously be delivered through the skin, but for phthalocyanines, systemic administration is more suitable. However, systemic administration places higher demands on advanced DDS, active tissue targeting and reduction of side effects. This review focuses on the already described liposomal DDS for phthalocyanines, but also describes examples of DDS used for structurally related PSs, which can be assumed to be applicable to phthalocyanines as well.
- Klíčová slova
- PDT, cancer, liposome, photosensitizer, phthalocyanine,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Chloramphenicol is an antibiotic with a broad spectrum of action and excellent tissue penetration. It had been widely used in clinical practice until the 1970s, but due to its potential myelotoxicity, it was gradually replaced by newly introduced antibiotics in the following years. The aim of the study was to find out to what extent and with what experience it is currently used in the Czech Republic. METHODS: A questionnaire survey was conducted in July and August 2022. The heads of all inpatient infectious diseases departments, hospital infectious diseases specialists and consulting microbiologists from antibiotic centers in large teaching hospitals without an infectious diseases department were asked to fill out the questionnaire. RESULTS: Thirty-five out of 39 hospitals contacted took part in the study, a response rate of 90 %. Chloramphenicol is used in 37 % of participating hospitals, with a frequency of up to 10 patients treated per year. The most common indications are brain abscesses, purulent meningitis, intra-abdominal, pelvic and lung abscesses, and polymicrobial infections with anaerobes. Chloramphenicol is almost always administered as an alternative antibiotic because of polyvalent allergy, bacterial resistance, and failure of previous treatment. Sixty-six percent of respondents described the effect as reliable or partially reliable, 34 % did not rate the effect. Fifty-two percent of respondents considered a dose of 8-9 g to be the maximum dose for an adult patient. In practice, 60 % of respondents did not encounter or could not assess the myelotoxic effects of chloramphenicol, 37 % observed reversible bone marrow suppression at least once, and only one respondent encountered aplastic anemia once. CONCLUSION: Unfortunately, chloramphenicol is currently used in less than half of hospitals in the Czech Republic. Because of its unique properties, it still has a place in today's anti-infective treatment. When properly indicated and after weighing the benefits and risks, it can be a suitable and sometimes life-saving alternative.
- MeSH
- antibakteriální látky škodlivé účinky MeSH
- antiinfekční látky * terapeutické užití MeSH
- bakteriální infekce * farmakoterapie MeSH
- chloramfenikol škodlivé účinky MeSH
- dospělí MeSH
- infekční nemoci * MeSH
- lidé MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- antiinfekční látky * MeSH
- chloramfenikol MeSH
BACKGROUND: COVID-19 pandemic has led to a loss of human life in millions and devastating socio-economic consequences worldwide. So far, vaccination is the most effective long-term strategy to control and prevent severe COVID-19 disease. The aim of the current study was to evaluate the humoral immune responses raised against the BNT162b2 vaccine in hospital healthcare workers. METHODS: Total number of 173 healthcare workers enrolled in the study. Their blood samples were collected in three different time intervals after the second SARS-CoV-2 vaccination and evaluated by the ELISA method to detect anti-spike protein IgM and IgG antibodies. The baseline characteristics of all participants were collected using questionnaires and were evaluated for finding any significant data. RESULTS: Our results demonstrated that the levels of antibodies were higher in the young group (21-30 years old) and also among male participants. Moreover, the highest levels of antibodies were detected from the group that received the third shot vaccination. CONCLUSIONS: Our results indicate that age, gender and third-dose vaccination can affect the levels of humoral immune responses against the BNT162b2 vaccine in healthcare workers.
- Klíčová slova
- BNT162b2, COVID-19, ELISA, SARS-CoV-2, antibody titer, mRNA vaccine, spike protein,
- Publikační typ
- časopisecké články MeSH
Aqueous solutions of some polymers exhibit a lower critical solution temperature (LCST); that is, they form phase-separated aggregates when heated above a threshold temperature. Such polymers found many promising (bio)medical applications, including in situ thermogelling with controlled drug release, polymer-supported radiotherapy (brachytherapy), immunotherapy, and wound dressing, among others. Yet, despite the extensive research on medicinal applications of thermoresponsive polymers, their biodistribution and fate after administration remained unknown. Thus, herein, they studied the pharmacokinetics of four different thermoresponsive polyacrylamides after intramuscular administration in mice. In vivo, these thermoresponsive polymers formed depots that subsequently dissolved with a two-phase kinetics (depot maturation, slow redissolution) with half-lives 2 weeks to 5 months, as depot vitrification prolonged their half-lives. Additionally, the decrease of TCP of a polymer solution increased the density of the intramuscular depot. Moreover, they detected secondary polymer depots in the kidneys and liver; these secondary depots also followed two-phase kinetics (depot maturation and slow dissolution), with half-lives 8 to 38 days (kidneys) and 15 to 22 days (liver). Overall, these findings may be used to tailor the properties of thermoresponsive polymers to meet the demands of their medicinal applications. Their methods may become a benchmark for future studies of polymer biodistribution.
- Klíčová slova
- LCST, biodistribution, poly(2,2-difluoroethyl)acrylamide, poly(N,N-diethylacrylamide), poly(N-acryloylpyrolidine), poly(N-isopropylacrylamide), polyacrylamide, rational polymer design,
- MeSH
- myši MeSH
- polymery * MeSH
- teplota MeSH
- tkáňová distribuce MeSH
- uvolňování léčiv MeSH
- voda * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- polymery * MeSH
- voda * MeSH
